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Series GSE274318 Query DataSets for GSE274318
Status Public on Aug 20, 2024
Title High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells
Organism Homo sapiens
Experiment type Other
Summary New approach methodologies (NAMs) aim to accelerate the pace of chemical risk assessment while simultaneously reducing cost and dependency on animal studies. High Throughput Transcriptomics (HTTr) is an emerging NAM in the field of chemical hazard evaluation for establishing in vitro points-of-departure and providing mechanistic insight. In the current study, 1,201 test chemicals were screened for bioactivity at eight concentrations using a 24-hour exposure duration in the human- derived U-2 OS osteosarcoma cell line with HTTr. Assay reproducibility was assessed using three reference chemicals that were screened on every assay plate. The resulting transcriptomics data were analyzed by aggregating signal from genes into signature scores using gene set enrichment analysis, followed by concentration-response modeling of signatures scores. Signature scores were used to predict putative mechanisms of action, and to identify biological pathway altering concentrations (BPACs). BPACs were consistent across replicates for each reference chemical, with replicate BPAC standard deviations as low as 5.6×10-3 µM, demonstrating the internal reproducibility of HTTr-derived potency estimates. BPACs of test chemicals showed modest agreement (R2 = 0.55) with existing phenotype altering concentrations from high throughput phenotypic profiling using Cell Painting of the same chemicals in the same cell line. Altogether, this HTTr based chemical screen contributes to an accumulating pool of publicly available transcriptomic data relevant for chemical hazard evaluation and reinforces the utility of cell based molecular profiling methods in estimating chemical potency and predicting mechanism of action across a diverse set of chemicals.
 
Overall design In a previous study, we established experimental and computational workflows for HTTr screening in a human cell model (Harrill et al., 2021). The TempO-Seq human whole transcriptome assay (Yeakley et al., 2017) was used to identify biological pathway altering concentrations (BPACs) and characterize the biological activity of test chemicals. The present study applies those methods to a much larger chemical space. Here, we screened 1201 unique chemicals from the ToxCast chemical collection in U-2 OS cells using HTTr and the similar experimental conditions as described previously (Harrill et al., 2021).
 
Contributor(s) Bundy JL, Everett LJ, Rogers JD, Nyffeler J, Byrd G, Culbreth M, Haggard DE, Word LJ, Chambers BA, Davidson-Fritz S, Harris F, Willis C, Paul-Friedman K, Shah I, Judson R, Harrill JA
Citation(s) 39159848
BioProject PRJNA1142456
Submission date Aug 08, 2024
Last update date Oct 22, 2024
Contact name Derik Evan Haggard
E-mail(s) haggard.derik@epa.gov
Organization name US EPA
Department ORD-CCTE-SCDCD-DMMB
Street address 109 TW Alexander Drive
City Durham
State/province North Carolina
ZIP/Postal code 27709
Country USA
 

TABLE OF SRA INFORMATION header descriptions
title
BioSample
SRA Experiment
processed data file

Data table
title BioSample SRA Experiment processed data file
UHRR_TC0000490_A01 SAMN42941540 SRX25525706 u2os_pg1_count_data.csv.gz
ETOP_8_10.000000uM_TC0000490_A02 SAMN42941541 SRX25525707 u2os_pg1_count_data.csv.gz
EPAPLT0202A14_6_10.000000uM_TC0000490_A03 SAMN42941542 SRX25526443 u2os_pg1_count_data.csv.gz
RA_8_1.000000uM_TC0000490_A04 SAMN42941543 SRX25525835 u2os_pg1_count_data.csv.gz
EPAPLT0202A06_5_3.000000uM_TC0000490_A05 SAMN42941544 SRX25526073 u2os_pg1_count_data.csv.gz
EPAPLT0202F18_6_10.000000uM_TC0000490_A06 SAMN42941545 SRX25525628 u2os_pg1_count_data.csv.gz
EPAPLT0202E12_7_30.000000uM_TC0000490_A07 SAMN42941546 SRX25526214 u2os_pg1_count_data.csv.gz
EPAPLT0202F16_5_3.000000uM_TC0000490_A08 SAMN42941547 SRX25525682 u2os_pg1_count_data.csv.gz
EPAPLT0202F12_5_3.000000uM_TC0000490_A09 SAMN42941548 SRX25526365 u2os_pg1_count_data.csv.gz
EPAPLT0202G12_4_1.000000uM_TC0000490_A10 SAMN42941549 SRX25525979 u2os_pg1_count_data.csv.gz
EPAPLT0202F22_3_0.300000uM_TC0000490_A11 SAMN42941550 SRX25525708 u2os_pg1_count_data.csv.gz
EPAPLT0202F16_6_10.000000uM_TC0000490_A12 SAMN42941551 SRX25526342 u2os_pg1_count_data.csv.gz
EPAPLT0202A06_4_1.000000uM_TC0000490_A13 SAMN42941552 SRX25526427 u2os_pg1_count_data.csv.gz
EPAPLT0202C11_5_3.000000uM_TC0000490_A14 SAMN42941553 SRX25526348 u2os_pg1_count_data.csv.gz
EPAPLT0202A06_8_100.000000uM_TC0000490_A15 SAMN42941554 SRX25525728 u2os_pg1_count_data.csv.gz
EPAPLT0202F12_6_10.000000uM_TC0000490_A16 SAMN42941555 SRX25526354 u2os_pg1_count_data.csv.gz
EPAPLT0202C03_1_0.029900uM_TC0000490_A17 SAMN42941556 SRX25525734 u2os_pg1_count_data.csv.gz
EPAPLT0202A06_6_10.000000uM_TC0000490_A18 SAMN42941557 SRX25526176 u2os_pg1_count_data.csv.gz
EPAPLT0202E11_6_10.100000uM_TC0000490_A19 SAMN42941558 SRX25526179 u2os_pg1_count_data.csv.gz
EPAPLT0202F18_4_1.000000uM_TC0000490_A20 SAMN42941559 SRX25526440 u2os_pg1_count_data.csv.gz

Total number of rows: 32886

Table truncated, full table size 2972 Kbytes.




Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE274318_metadata.xlsx 3.6 Mb (ftp)(http) XLSX
GSE274318_u2os_pg10_count_data.csv.gz 23.0 Mb (ftp)(http) CSV
GSE274318_u2os_pg11_count_data.csv.gz 23.3 Mb (ftp)(http) CSV
GSE274318_u2os_pg12_count_data.csv.gz 22.7 Mb (ftp)(http) CSV
GSE274318_u2os_pg13_count_data.csv.gz 22.9 Mb (ftp)(http) CSV
GSE274318_u2os_pg14_count_data.csv.gz 23.0 Mb (ftp)(http) CSV
GSE274318_u2os_pg15_count_data.csv.gz 23.2 Mb (ftp)(http) CSV
GSE274318_u2os_pg16_count_data.csv.gz 23.1 Mb (ftp)(http) CSV
GSE274318_u2os_pg17_count_data.csv.gz 23.5 Mb (ftp)(http) CSV
GSE274318_u2os_pg18_count_data.csv.gz 23.5 Mb (ftp)(http) CSV
GSE274318_u2os_pg19_count_data.csv.gz 22.8 Mb (ftp)(http) CSV
GSE274318_u2os_pg1_count_data.csv.gz 23.4 Mb (ftp)(http) CSV
GSE274318_u2os_pg20_count_data.csv.gz 23.4 Mb (ftp)(http) CSV
GSE274318_u2os_pg21_count_data.csv.gz 23.1 Mb (ftp)(http) CSV
GSE274318_u2os_pg22_count_data.csv.gz 23.4 Mb (ftp)(http) CSV
GSE274318_u2os_pg23_count_data.csv.gz 23.2 Mb (ftp)(http) CSV
GSE274318_u2os_pg24_count_data.csv.gz 23.0 Mb (ftp)(http) CSV
GSE274318_u2os_pg25_count_data.csv.gz 23.4 Mb (ftp)(http) CSV
GSE274318_u2os_pg26_count_data.csv.gz 23.1 Mb (ftp)(http) CSV
GSE274318_u2os_pg27_count_data.csv.gz 23.5 Mb (ftp)(http) CSV
GSE274318_u2os_pg28_count_data.csv.gz 23.0 Mb (ftp)(http) CSV
GSE274318_u2os_pg29_count_data.csv.gz 23.1 Mb (ftp)(http) CSV
GSE274318_u2os_pg2_count_data.csv.gz 23.5 Mb (ftp)(http) CSV
GSE274318_u2os_pg3_count_data.csv.gz 23.1 Mb (ftp)(http) CSV
GSE274318_u2os_pg4_count_data.csv.gz 23.1 Mb (ftp)(http) CSV
GSE274318_u2os_pg5_count_data.csv.gz 23.5 Mb (ftp)(http) CSV
GSE274318_u2os_pg6_count_data.csv.gz 22.8 Mb (ftp)(http) CSV
GSE274318_u2os_pg7_count_data.csv.gz 23.5 Mb (ftp)(http) CSV
GSE274318_u2os_pg8_count_data.csv.gz 23.0 Mb (ftp)(http) CSV
GSE274318_u2os_pg9_count_data.csv.gz 23.2 Mb (ftp)(http) CSV

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